title: Selaginellatamariscina attenuates metastasis via Akt pathways in oral cancer cells.
abstract: BACKGROUND
  Crude extracts of Selaginellatamariscina, an oriental medicinal herb, have been evidenced to treat several human diseases. This study investigated the mechanisms by which Selaginellatamariscina inhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells.
  
  
  RESULTS
  Herein, we demonstrate that Selaginellatamariscina attenuated HSC-3 cell migration and invasion in a dose-dependent manner. The anti-metastatic activities of Selaginellatamariscina occurred at least partially because of the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 gelatinase activity and the down-regulation of protein expression. The expression and function of both MMP-2 and MMP-9 were regulated by Selaginellatamariscina at a transcriptional level, as shown by quantitative real-time PCR and reporter assays. Chromatin immunoprecipitation (ChIP) data further indicated that binding of the cAMP response element-binding (CREB) protein and activating protein-1 (AP-1) to the MMP-2 promoter diminished at the highest dosage level of Selaginellatamariscina. The DNA-binding activity of specificity protein 1 (SP-1) to the MMP-9 promoter was also suppressed at the same concentration. Selaginellatamariscina did not affect the mitogen-activated protein kinase signaling pathway, but did inhibit the effects of gelatinase by reducing the activation of serine-threonine kinase Akt.
  
  
  CONCLUSIONS
  These results demonstrate that Selaginellatamariscina may be a potent adjuvant therapeutic agent in the prevention of oral cancer.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jia-Sin
authors.initials: JS
authors.lastname: Yang
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Hsin
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D032503:Selaginellaceae / Q000737:chemistry*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9